Berditsch Marina, Lux Hannah, Babii Oleg, Afonin Sergii, Ulrich Anne S
Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, Karlsruhe 76131, Germany.
Institute of Biological Interfaces (IBG-2), KIT, P. O. Box 3640, Karlsruhe 76021, Germany.
Pharmaceuticals (Basel). 2016 Sep 7;9(3):56. doi: 10.3390/ph9030056.
An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired tetracycline resistance. In these cases, root canal infections are commonly treated with Ledermix(®) paste, which contains demeclocycline, or the new alternative endodontic paste Odontopaste, which contains clindamycin; however, these treatments are often ineffective. We studied the killing activity of the cyclic antimicrobial peptide gramicidin S (GS) against planktonic and biofilm cells of tetracycline-resistant clinical isolates of E. faecalis. The high therapeutic potential of GS for the topical treatment of problematic teeth is based on the rapid bactericidal effect toward the biofilm-forming, tetracycline-resistant E. faecalis. GS reduces the cell number of planktonic cells within 20-40 min at a concentration of 40-80 μg/mL. It kills the cells of pre-grown biofilms at concentrations of 100-200 μg/mL, such that no re-growth is possible. The translocation of the peptide into the cell interior and its complexation with intracellular nucleotides, including the alarmon ppGpp, can explain its anti-biofilm effect. The successful treatment of persistently infected root canals of two volunteers confirms the high effectiveness of GS. The broad GS activity towards resistant, biofilm-forming E. faecalis suggests its applications for approval in root canal medication.
耐克林霉素的粪肠球菌是根管治疗失败后牙齿中最常见的单一菌种，通常还具有获得性四环素耐药性。在这些情况下，根管感染通常用含有地美环素的Ledermix（®）糊剂或含有克林霉素的新型替代牙髓糊剂Odontopaste进行治疗；然而，这些治疗往往无效。我们研究了环抗菌肽短杆菌肽S（GS）对四环素耐药临床分离粪肠球菌浮游细胞和生物膜细胞的杀伤活性。GS用于局部治疗有问题牙齿的高治疗潜力基于其对形成生物膜的四环素耐药粪肠球菌的快速杀菌作用。GS在40-80μg/mL浓度下20-40分钟内可减少浮游细胞数量。它在100-200μg/mL浓度下可杀死预生长生物膜的细胞，从而使其无法再生长。该肽向细胞内部的转运及其与包括警报素ppGpp在内的细胞内核苷酸的络合可以解释其抗生物膜作用。两名志愿者持续感染根管的成功治疗证实了GS的高效性。GS对耐药、形成生物膜的粪肠球菌的广泛活性表明其在根管用药中具有获批应用的潜力。
